Multidimensional mass spectrometry of serum and cellular lipids directly from biologic extracts

Abstract

A method for determination of at least one of the lipid species in a biological sample comprising subjecting the sample to lipid extraction to obtain a lipid extract and subjecting the resulting lipid extract to multidimensional electrospray ionization mass spectrometry using either precursor ion or neutral loss scanning (or both) of all naturally occurring aliphatic chains, lipid fragments and precursor ions leading to observed fragments to generate a multidimensional matrix whose contour densities provides structural and quantitative information directly without chromatography. A method for determination of lipid content and/or lipid molecular species composition and quantity directly from lipid extracts of a biological sample comprising subjecting said lipid extract to electrospray ionization multidimensional mass spectrometry by comparisons to standards and algorithms described herein.

Description

CROSS REFERENCE TO RELATED APPLICATION[0001]This application is a continuation in part of pending U.S. nonprovisional patent application Ser. No. 10 / 606,601, filed Jun. 26, 2003 now U.S. Pat. No. 7,306,952 which claims priority to U.S. provisional patent application 60 / 391,711 filed Jun. 26, 2002, and claims the benefit of U.S. provisional patent application 60 / 458,733 filed Mar. 28, 2003 all of which are incorporated by reference in their entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH & DEVELOPMENT[0002]This work was supported by grants from NIH including grants W / H P01 HL57278 / JDFI 996003, R02HL41250, RO1 AA11094, P41-RR00954, P60-DK20579, and P30-DK56341. The government has certain rights in the invention.FIELD OF THE INVENTION[0003]This invention relates generally to a method of analysis for lipids including triglycerides and other mentioned cellular lipids in a biological sample. More particularly this invention relates to a method for analysis and individual molecul...

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Benefits of technology

[0026]In an aspect, a method for determining an agent which selectively targets lipid i.e. triglyceride molecular species (e.g., saturated triglycerides) comprises analyzing a biological sample of at least one individual for TG molecular species determination, administering a therapeutic amount of a drug to the individual, analyzing a biological sample of said administered individual for TG molecular species determination, comparing the TG molecular species determination after said administration with the TG molecular species determination prior to the drug administration and determining an effect if any on the individual of the drug administration. In an aspect, the comparison of the TG molecular species determination of the biological samples is indicative of development of the condition for that (treated) individual.

[0027]In an aspect, a method of identifying a candidate lipid modulating drug having lipid modulating drug efficacy comprises selecting a biological sample to be taken, analyzing a biological sample of at least one individual for lipid i.e. TG molecular species determination, administering of a candidate lipid modulating drug to the individual, analyzing a biological sample of treated individual, comparing the TG molecular species determination after said administration with the TG molecular species determination prior to the drug administration and determining an effect on the individual of the drug administration. In an aspect, the comparison of TG analysis is indicative of the efficacy a lipid modulating capacity of an administered drug.

[0028]In an a

Problems solved by technology

Additionally, such afflictions destroy or significantly reduce the quality of life even if not immediately fatal.

Although some studies have measured total TG molecular species content in multiple different disease states, a paucity of information on TG molecular species changes during pathophysiological alterations is available.

Previous attempts at direct TG quantitation by positive-ion electrospray

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